July 5, 2019 0 By FM

Three-year-old Feroz (name changed), was brought to Surya Hospitals, Mumbai, after complaining of limb pain and low-grade fever for over a fortnight. A hip X-ray was completely normal as were the complete blood count results. The only alarming result was a low neutrophil count. Considering the persistent limb pain in combination with the low neutrophil counts, Dr Mukesh Desai, Director of Department of Hematology, Oncology and Immunology, was consulted. He advised a bone marrow investigation which identified the presence of lymphoblasts and confirmed the diagnosis to be acute lymphoblastic leukaemia (ALL), one of the commonest paediatric cancers.

ALL is typically diagnosed in children 2-10 years of age and very rarely seen in younger or older children. Bleeding, bruises, repeated infections and severe bone pain are often symptoms of ALL. These symptoms may also be accompanied with shortness of breath, fever, enlarged spleen and lymph nodes, and low haemoglobin, platelet and neutrophil levels. Diagnostic tests include complete blood counts and bone marrow investigations. Specialized tests, including a morphologic assessment, immunophenotyping and cytogenetics are performed on bone marrow aspirates. Immunophenotyping and cytogenetic studies help to classify the type of leukaemia into B cell or T cell leukaemias. They are also important to classify the patients into standard-risk or high-risk, thereby aiding to evaluate the prognosis and to customize treatment options.

Morphological bone marrow assessment can help to distinguish between myeloblasts and lymphoblasts. The presence of at least 20% of blast cells is indicative of ALL. Such an assessment is, however, insufficient to determine whether the lymphoblasts are of B cell or T cell origin and immunophenotyping is required. Cytogenetics aid to determine the changes in chromosomes and help in the prognosis and deciding the treatment modalities.

For Feroz, immunophenotyping revealed the involvement of pre-B cells and cytogenetics showed a chromosomal translocation. Such a B cell ALL had good prognosis, especially at this early detection stage, and Feroz was categorized into the standard-risk category.

Treatment is typically multi-phased into induction, consolidation, and maintenance phases. The primary goal of the first phase is to achieve complete remission within 4-6 weeks of therapy. During this induction phase,

the child is given different combinations of chemo drugs. At the end of the induction phase, the child should become clinically normal. Any liver or spleen enlargement, as well as blood and bone marrow abnormalities, should revert to normal with 99% cancer under control. Complete remission is also assessed by determining the minimal residual disease (MRD). MRD indicates the presence of cancer cells which typically causes a relapse or recurrence of leukaemia. For complete remission, MRD should be negative, to show that the cancer is under control. If MRD is positive, it indicates a poor prognosis and the child is placed in the high-risk category. If the child goes into remission, the consolidation phase often consists of treatment with the same drugs at high doses. However, if the patient is

considered to be high-risk, is not undergoing remission or undergoes a relapse, bone marrow transplant may be recommended. The consolidation phase includes extended induction, high-dose methotrexate and re-induction phases. It typically lasts for 6 months. This is followed by the last phase, the maintenance phase, which usually continues for up to 2 years.

Feroz was initially started on steroids and was monitored for tumour lysis, which causes electrolyte imbalances and metabolic disturbances such as a drop in calcium levels and increases in potassium and phosphorous levels. These changes can be detrimental to the child and must be corrected in time. Feroz received the 4-drug induction therapy following the Berlin-Frankfurt-Münster (BFM) protocol. The chemo drugs included steroids, vincristine, daunorubicin, and L-asparaginase. By 6 weeks, while Feroz’s bone marrow was normal, his MRD was still positive. He was then placed in an intermediate risk

category and chemotherapy doses were intensified during the extended induction phase or consolidation phase. A repeat MRD 6 weeks later was found to be negative.

He is now about to start on the maintenance phase of treatment and will be on chemo for an additional one and a half years.

Most of Feroz’s treatment was done on an OPD basis to cut down costs and decrease chances of infection. He required hospitalization only during the induction phase, for 3-5 days every 3 weeks. Feroz was admitted for febrile neutropenia and had to be given multi-antibiotics IV for 8-9 days each time. Granulocyte colony stimulating factor injections also had to be given to stimulate WBCs faster. Feroz is doing well and has an 80% chance of being completely cured.

Dr Desai advocates the need for accurate and timely diagnosis for better outcomes and recommends that doctors should consider ALL for any child who presents with limb pain or bone pain and is not able to walk. While interpreting CBC, if neutrophils are low, even though platelet counts may be normal, a bone marrow investigation should be done to rule out blood cancer. As per Dr Desai, “Half a century ago the cure rate for ALL was only 10%. However, today, 80-90% of all children with ALL are cured. Newer treatment modalities are constantly being evaluated for better outcomes and the aim is to achieve a 95% cure rate.’